After a traumatic spinal cord injury (SCI), recovery of independent ambulation is one of the most important goals for patients during rehabilitation. Most will not recover the ability to walk or will step slowly at a high energy cost that prevents community mobility. No particular rehabilitation strategy has been shown to be better than another at improving locomotor functional independence or maximizing walking speed. We propose the first multicenter, randomized clinical trial (RCT) of a task-oriented locomotor intervention for acute SCI. This strategy applies basic neuroscience research and pilot clinical studies about use-dependent locomotor learning in the lumbosacral neural circuits and supraspinal neurons that coordinate leg movements. The intervention, called body weight-supported treadmill training (BWSTT), partially supports the weight of patients via an overhead lift attached to a harness worn by the subject. Therapists can then systematically train patients to walk on a treadmill at increasingly more functional speeds with less weight support. They correct gait deviations and manipulate sensory inputs that enhance control of the stance and swing phases of walking. For the proposed trial, therapists at 5 outstanding SCI rehabilitation centers will be trained in the technique. The University of California Los Angeles coordinating and data management center will randomly assign eligible subjects over the next 2 years to a conventional therapy program for mobility versus the same intensity and duration of a combination of conventional therapy plus BWSTT. One hundred subjects with incomplete SCI from below C4 to T10/11 and 100 subjects with lesions at T12 to L3 will be entered within 5 weeks of a SCI and treated for 12 weeks. The two primary outcome measures are the level of independence for ambulation and the maximal speed for walking 50 feet, tested after 12 weeks of therapy and 6 and 12 months after randomization. The results will also be relevant to people with chronic or complete SCI who, in the future, may receive biologic interventions combined with locomotor training. In addition, it will demonstrate the value and feasibility of the RCT for developing evidence-based rehabilitation practices.